Abstract This project aimed at developing nanovesicles of econazole nitrate (EN) and formulating them as a suitable dermatological gel for improved therapeutic efficacy, better dispersity, and good storage stability. Ethosomes were prepared by cold method and evaluated for the mean diameter, surface charge, and entrapment efficiency. Optimized ethosomes with vesicle size and entrapment efficiency of 202.85 ± 5.10 nm and 81.05 ± 0.13%, respectively, were formulated as Carbopol 934 NF gels with varied permeation enhancers (G1–G7), and compared with liposomal and hydroethanolic gels. The pharmacotechnical evaluation of gels demonstrated G6 with a flux rate of 0.46 ± 0.22 μg/cm2 hr 1/ 2 as the best formulation that was able to exhibit controlled release of EN for 12 hours across rat skin, and percent drug diffused from ethosomes was nearly twofold higher than liposomal and hydroethanolic gels. Confocal laser scanning microscopy demonstrated drug permeation as far as the last layer of epidermis (stratum basale). Stability profile of the prepared system assessed for 180 days revealed very low aggregation and insignificant growth in vesicular size. The results collectively suggest that because of the controlled drug release, better antifungal activity, and good storage stability, EN ethosomal gel has tremendous potential to serve as a topical delivery system. From the Clinical Editor Ethosomal gel of econazole nitrate was found to have outstanding potential to serve as a topical delivery system, enabling controlled drug release, providing better antifungal activity, and good storage stability.